Particle Trap Paves Way for Personalized Medicine

But being able to isolate individual molecules like DNA base pairs, which are just two nanometers across -- or about 1/50,000th the diameter of a human hair -- is incredibly expensive and difficult to control. In addition, devising a way to trap DNA molecules in their natural aqueous environment further complicates things. Scientists have spent the past decade struggling to isolate and trap individual DNA molecules in an aqueous solution by trying to thread it through a tiny hole the size of DNA, called a"nanopore," which is exceedingly difficult to make and control.

Now a team led by Yale University researchers has proven that isolating individual charged particles, like DNA molecules, is indeed possible using a method called"Paul trapping," which uses oscillating electric fields to confine the particles to a space only nanometers in size. (The technique is named for Wolfgang Paul, who won the Nobel Prize for the discovery.) Until now, scientists have only been able to use Paul traps for particles in a vacuum, but the Yale team was able to confine a charged test particle -- in this case, a polystyrene bead -- to an accuracy of just 10 nanometers in aqueous solutions between quadruple microelectrodes that supplied the electric field.

Their device can be contained on a single chip and is simple and inexpensive to manufacture."The idea would be that doctors could take a tiny drop of blood from patients and be able to run diagnostic tests on it right there in their office, instead of sending it away to a lab where testing can take days and is expensive," said Weihua Guan, a Yale engineering graduate student who led the project.

In addition to diagnostics, this"lab-on-a-chip" would have a wide range of applications, Guan said, such as being able to analyze how individual cells respond to different stimulation. While there are several other techniques for cell-manipulation available now, such as optical tweezers, the Yale team's approach actually works better as the size of the targets gets smaller, contrary to other approaches.

The team, whose findings appear in the May 23 Early Edition of theProceedings of the National Academy of Sciences,used charged polystyrene beads rather than actual DNA molecules, along with a two-dimensional trap to prove that the technique worked. Next, they will work toward creating a 3-D trap using DNA molecules, which, at two nanometers, are even smaller than the test beads. They hope to have a working, 3-D trap using DNA molecules in the next year or two. The project is funded by a National Institutes of Health program that aims to sequence a patient's entire genome for less than$1,000.

"This is the future of personalized medicine," Guan said.

The project was directed by Mark Reed (Yale University) and Predrag Krstic (Oak Ridge National Laboratory). Other authors of the paper include Sony Joseph and Jae Hyun Park (Oak Ridge National Laboratory).

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Laser Modules in Matchbox Size

Compact laser modules from the Berlin-based Ferdinand-Braun-Institut (FBH) which are only the size of a matchbox open up various application areas. The flexible all-rounders can be optimized according to the specific demands made on lasers in material analytics, display technology as well as material processing.

The modules consist of several optoelectronic semiconductor chips (diode laser and amplifier) and adapted gallium nitride transistors. All chips have been developed at FBH and base on the institute's comprehensive know-how in semiconductor technology and chip development. Additionally, hybrid-integrated micro optics and non-linear crystals form the beam and transform the wavelength into the blue and green spectral region respectively. Within this spectral region, the modules now reach output powers exceeding 1.5 W with an excellent beam quality. Using a single-pass configuration enables simple frequency doubling and thus modules which can be realized specifically compact. They are particularly suitable for applications requiring low-noise performance, this means with as little undesired signals as possible, and fast modulation.

Efficient, pulsed laser beam sources offering high flexibility

The FBH additionally presents diode lasers which are, due to their flexibility, preferably used in laser systems for material processing. Mobile short-range LIDAR systems may also benefit from the efficient and compact diode lasers. One of such sources is a newly developed miniaturized pulsed laser module with 10 ps… 100 ns pulse width and a defined repetition rate in the kHz and MHz range. FBH also introduces these lasers at the accompanying symposium. With hybrid-integrated amplifiers they reach peak powers up to several 10 W.

With its gain-switching 1064 nm DFB laser diodes assembled with integrated electronics in a butterfly housing, which FBH showcases at the fair for the first time, the institute introduces further flexible light sources for the 1-100 ns time-domain. Without amplifier, their pulse powers are at 1.5 W in the time range 1-10 ns.

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Toward Faster Transistors: Physicists Discover Physical Phenomenon That Could Boost Computers' Clock Speed

In this week's issue of the journalScience,MIT researchers and their colleagues at the University of Augsburg in Germany report the discovery of a new physical phenomenon that could yield transistors with greatly enhanced capacitance -- a measure of the voltage required to move a charge. And that, in turn, could lead to the revival of clock speed as the measure of a computer's power.

In today's computer chips, transistors are made from semiconductors, such as silicon. Each transistor includes an electrode called the gate; applying a voltage to the gate causes electrons to accumulate underneath it. The electrons constitute a channel through which an electrical current can pass, turning the semiconductor into a conductor.

Capacitance measures how much charge accumulates below the gate for a given voltage. The power that a chip consumes, and the heat it gives off, are roughly proportional to the square of the gate's operating voltage. So lowering the voltage could drastically reduce the heat, creating new room to crank up the clock.

MIT Professor of Physics Raymond Ashoori and Lu Li, a postdoc and Pappalardo Fellow in his lab -- together with Christoph Richter, Stefan Paetel, Thilo Kopp and Jochen Mannhart of the University of Augsburg -- investigated the unusual physical system that results when lanthanum aluminate is grown on top of strontium titanate. Lanthanum aluminate consists of alternating layers of lanthanum oxide and aluminum oxide. The lanthanum-based layers have a slight positive charge; the aluminum-based layers, a slight negative charge. The result is a series of electric fields that all add up in the same direction, creating an electric potential between the top and bottom of the material.

Ordinarily, both lanthanum aluminate and strontium titanate are excellent insulators, meaning that they don't conduct electrical current. But physicists had speculated that if the lanthanum aluminate gets thick enough, its electrical potential would increase to the point that some electrons would have to move from the top of the material to the bottom, to prevent what's called a"polarization catastrophe." The result is a conductive channel at the juncture with the strontium titanate -- much like the one that forms when a transistor is switched on. So Ashoori and his collaborators decided to measure the capacitance between that channel and a gate electrode on top of the lanthanum aluminate.

They were amazed by what they found: Although their results were somewhat limited by their experimental apparatus, it may be that an infinitesimal change in voltage will cause a large amount of charge to enter the channel between the two materials."The channel may suck in charge -- shoomp! Like a vacuum," Ashoori says."And it operates at room temperature, which is the thing that really stunned us."

Indeed, the material's capacitance is so high that the researchers don't believe it can be explained by existing physics."We've seen the same kind of thing in semiconductors," Ashoori says,"but that was a very pure sample, and the effect was very small. This is a super-dirty sample and a super-big effect." It's still not clear, Ashoori says, just why the effect is so big:"It could be a new quantum-mechanical effect or some unknown physics of the material."

There is one drawback to the system that the researchers investigated: While a lot of charge will move into the channel between materials with a slight change in voltage, it moves slowly -- much too slowly for the type of high-frequency switching that takes place in computer chips. That could be because the samples of the material are, as Ashoori says,"super dirty"; purer samples might exhibit less electrical resistance. But it's also possible that, if researchers can understand the physical phenomena underlying the material's remarkable capacitance, they may be able to reproduce them in more practical materials.

Triscone cautions that wholesale changes to the way computer chips are manufactured will inevitably face resistance."So much money has been injected into the semiconductor industry for decades that to do something new, you need a really disruptive technology," he says.

"It's not going to revolutionize electronics tomorrow," Ashoori agrees."But this mechanism exists, and once we know it exists, if we can understand what it is, we can try to engineer it."

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Forecast Calls for Nanoflowers to Help Return Eyesight: Physicist Leads Effort to Design Fractal Devices to Put in Eyes

These flowers are not roses, tulips or columbines. They will be nanoflowers seeded from nano-sized particles of metals that grow, or self assemble, in a natural process -- diffusion limited aggregation. They will be fractals that mimic and communicate efficiently with neurons.

Fractals are"a trademark building block of nature," Taylor says. Fractals are objects with irregular curves or shapes, of which any one component seen under magnification is also the same shape. In math, that property is self-similarity. Trees, clouds, rivers, galaxies, lungs and neurons are fractals, Taylor says. Today's commercial electronic chips are not fractals, he adds.

Eye surgeons would implant these fractal devices within the eyes of blind patients, providing interface circuitry that would collect light captured by the retina and guide it with almost 100 percent efficiency to neurons for relay to the optic nerve to process vision.

In an article titled"Vision of beauty" forPhysics World, Taylor, a physicist and director of the UO Materials Science Institute, describes his envisioned approach and how it might overcome the problems occurring with current efforts to insert photodiodes behind the eyes. Current chip technology is limited, because it doesn't allow sufficient connections with neurons.

"The wiring -- the neurons -- in the retina is fractal, but the chips are not fractal," Taylor says."They are just little squares of electrodes that provide too little overlap with the neurons."

Beginning this summer, Taylor's doctoral student Rick Montgomery will begin a yearlong collaboration with Simon Brown at the University of Canterbury in New Zealand to experiment with various metals to grow the fractal flowers on implantable chips.

The idea for the project emerged as Taylor was working under a Cottrell Scholar Award he received in 2003 from the Research Corporation for Science Advancement. His vision is now beginning to blossom under grants from the Office of Naval Research (ONR), the U.S. Air Force and the National Science Foundation.

Taylor's theoretical concept for fractal-based photodiodes also is the focus of a U.S. patent application filed by the UO's Office of Technology Transfer under Taylor's and Brown's names, the UO and University of Canterbury.

The project, he writes in thePhysics Worldarticle, is based on"the striking similarities between the eye and the digital camera." (Physics Worldarticle is available at:http://physicsworld.com/cws/article/indepth/45840)

"The front end of both systems," he writes,"consists of an adjustable aperture within a compound lens, and advances bring these similarities closer each year." Digital cameras, he adds, are approaching the capacity to capture the 127 megapixels of the human eye, but current chip-based implants, because of their interface, are only providing about 50 pixels of resolution.

Among the challenges, Taylor says, is determining which metals can best go into body without toxicity problems."We're right at the start of this amazing voyage," Taylor says."The ultimate thrill for me will be to go to a blind person and say, we're developing a chip that one day will help you see again. For me, that is very different from my previous research, where I've been looking at electronics to go into computers, to actually help somebody… if I can pull that off that will be a tremendous thrill for me."

Taylor also is working under a Research Corp. grant to pursue fractal-based solar cells.

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Optical Microscope Without Lenses Produces High-Resolution 3-D Images on a Chip

The advance, featured in the early online edition of the journalProceedings of the National Academy of Sciences, represents the first demonstration of lens-free optical tomographic imaging on a chip, a technique capable of producing high-resolution 3-D images of large volumes of microscopic objects.

"This research clearly shows the potential of lens-free computational microscopy," said Aydogan Ozcan, senior author of the research and an associate professor of electrical engineering at UCLA's Henry Samueli School of Engineering and Applied Science."Wonderful progress has been made in recent years to miniaturize life-sciences tools with microfluidic and lab-on-a-chip technologies, but until now optical microscopy has not kept pace with the miniaturization trend."

An optical imaging system small enough to fit onto an opto-electronic chip provides a variety of benefits. Because of the automation involved in on-chip systems, scientific work could be sped up significantly, which might have a great impact in the fields of cell and developmental biology. In addition, the small size not only has great potential for miniaturizing systems but also leads to cost savings on equipment.

The optical microscope, invented more than 400 years ago, has tended to grow larger and more complex as it has been modified to image ever-smaller objects with better resolution. To address this lack of progress in miniaturization, Ozcan's research group -- with graduate student Serhan Isikman and postdoctoral scholar Waheb Bishara as lead researchers -- developed the new tomographic microscopy platform through the next evolution of a lens-free imaging technology the group created and has been improving for years.

Ozcan, a researcher at the California NanoSystems Institute at UCLA, makes the analogy that a traditional optical microscope is like a huge set of pipes delivering content, in the form of images, to the user. Over years of development, bottlenecks occur that impede further improvement. Even if one part of the system -- that is, one bottleneck -- is improved, other bottlenecks keep that improvement from being fully realized. Not so with the lens-free system, according to Ozcan.

"Lens-free imaging removes the pipes altogether by utilizing an entirely new design," he said.

The system takes advantage of the fact that organic structures, such as cells, are partially transparent. So by shining a light on a sample of cells, the shadows created reveal not only the cells' outlines but details about their sub-cellular structures as well.

"These details can be captured and analyzed if the shadow is directed onto a digital sensor array," Isikman said."The end result of this process is an image taken without using a lens."

Ozcan envisions this lens-free imaging system as one component in a lab-on-a-chip platform. It could potentially fit beneath a microfluidic chip, a tool for the precise control and manipulation of sub-millimeter biological samples and fluids, and the two tools would operate in tandem, with the microfluidic chip depositing and subsequently removing a sample from the lens-free imager in an automated, or high-throughput, process.

The platform's 3-D images are created by rotating the light source to illuminate the samples from multiple angles. These multiple angles also allow the system to utilize tomography, a powerful imaging technique. Through the use of tomography, the system is able to produce 3-D images without sacrificing resolution.

"The field of view of lens-based microscopes is limited because the lens focuses on a narrow area of a sample," Bishara said."A lens-free microscope has both a much larger field of view and depth of field because the imaging is done by the digital sensor array and is not constrained by a lens."

The research was funded by grants from the National Science Foundation, the U.S. Office of Naval Research and the National Institutes of Health and was also supported by the Gates Foundation and the Vodafone Americas Foundation.

For more information on the Ozcan research group, visithttp://innovate.ee.ucla.edu/.

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Controlled Production of Nanometric Drops

The study details the different physical conditions needed to destabilize a fluid and create droplets according to the wetting properties of the surface it is in contact with. Ignasi Pagonabarraga, a lecturer with the Department of Fundamental Physics and one of the authors of the study, explains that"the interaction of the fluid with the surface can be used to control the size of the drops and the time they take to form. Although there are other methods for creating micrometric droplets, the affinity of liquids to solid surfaces creates a more versatile environment for the production and control of drops down to the nanoscale."

According to Aurora Hernández-Machado, a lecturer with the UB's Department of Structure and Constituents of Matter and co-author of the study,"miniaturization in liquids is important in increasing efficiency and optimizing the rate of consumption of substances such as pharmaceutical products, cosmetics and ink, which would enable us to lower the cost of processes associated with the production and control of these products. In addition, the physical model, which we could define as a microfluidic dispenser for various substances, allows us to overcome the limitations traditionally associated with drop formation processes and to create submicrometre-scale droplets."

One of the fields to which this type of process is most readily applicable is the development of lab-on-a-chip (LOC) devices, which integrate a range of laboratory analysis functions into a miniaturized chip format and need only very small volumes of liquid to perform the analyses. The dynamics involved in the formation of submicrometre-scale drops have various technological applications in other fields, for example in controlled drug administration or in the creation of emulsions such as those used in certain types of cosmetic products formed by micro-droplets of substances with specific properties within another fluid. Other applications include ink distribution in printers.

In physical terms, the drops are formed due to instability in the fluid. The study describes a wetting-based destabilization mechanism of forced microfilaments that affects adherence to difference surfaces. The researchers have been able to establish the balance of forces that determines the drop emission mechanism, which involves the capillarity of the fluid, the viscous friction of the solid surface and gravity. This balance and the size of the liquid filaments determine the size of the drops emitted, which in some cases are nanometric. It has also been observed that the emission of drops depends to a great extent on the static wetting angle, that is, the angle that the drop makes with the contact surface. The greater this angle the higher the degree of hydrophobia of the surface in question.

In the experiments carried out for the study, focusing on water in air, the team of researchers has demonstrated the operation of the microfluidic model and created drops at the micrometre scale, but the model is also capable of producing nanometric droplets. Tests have been carried out using a range of supports from hydrophilic surfaces to superhydrophobic substrates, and the authors show how wetting can be used to pinpoint the wetting-controlled emission point. By varying the chemical and nanostructural properties of the surface in question, it is possible to alter the wetting angle and control the drop formation dynamics.

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First Macro-Scale Thin-Film Solid-Oxide Fuel Cell: Strong, Nanostructured Membrane Enables Scaling for Clean-Energy Applications

While SOFCs have previously worked at the micro-scale, this is the first time any research group has overcome the structural challenges of scaling the technology up to a practical size with a proportionally higher power output.

Reported online April 3 inNature Nanotechnology, the demonstration of this fully functional SOFC indicates the potential of electrochemical fuel cells to be a viable source of clean energy.

"The breakthrough in this work is that we have demonstrated power density comparable to what you can get with tiny membranes, but with membranes that are a factor of a hundred or so larger, demonstrating that the technology is scalable," says principal investigator Shriram Ramanathan, Associate Professor of Materials Science at SEAS.

SOFCs create electrical energy via an electrochemical reaction that takes place across an ultra-thin membrane. This 100-nanometer membrane, comprising the electrolyte and electrodes, has to be thin enough to allow ions to pass through it at a relatively low temperature (which, for ceramic fuel cells, lies in the range of 300 to 500 degrees Celsius). These low temperatures allow for a quick start-up, a more compact design, and less use of rare-earth materials.

So far, however, thin films have been successfully implemented only in micro-SOFCs, where each chip in the fuel cell wafer is about 100 microns wide. For practical applications, such as use in compact power sources, SOFCs need to be about 50 times wider.

The electrochemical membranes are so thin that creating one on that scale is roughly equivalent to making a 16-foot-wide sheet of paper. Naturally, the structural issues are significant.

"If you make a conventional thin membrane on that scale without a support structure, you can't do anything -- it will just break," says co-author Bo-Kuai Lai, a postdoctoral fellow at SEAS."You make the membrane in the lab, but you can't even take it out. It will just shatter."

With lead author Masaru Tsuchiya (Ph.D. '09), a former member of Ramanathan's lab who is now at SiEnergy, Ramanathan and Lai fortified the thin film membrane using a metallic grid that looks like nanoscale chicken wire.

The tiny metal honeycomb provides the critical structural element for the large membrane while also serving as a current collector. Ramanathan's team was able to manufacture membrane chips that were 5 mm wide, combining hundreds of these chips into palm-sized SOFC wafers.

While other researchers' earlier attempts at implementing the metallic grid showed structural success, Ramanathan's team is the first to demonstrate a fully functional SOFC on this scale. Their fuel cell's power density of 155 milliwatts per square centimeter (at 510 degrees Celsius) is comparable to the power density of micro-SOFCs.

When multiplied by the much larger active area of this new fuel cell, that power density translates into an output high enough for relevance to portable power.

Previous work in Ramanathan's lab has developed micro-SOFCs that are all-ceramic or that use methane as the fuel source instead of hydrogen. The researchers hope that future work on SOFCs will incorporate these technologies into the large-scale fuel cells, improving their affordability.

In the coming months, they will explore the design of novel nanostructured anodes for hydrogen-alternative fuels that are operable at these low temperatures and work to enhance the microstructural stability of the electrodes.

The research was supported in part by the National Science Foundation (NSF) and performed in part at the Harvard University Center for Nanoscale Systems, a member of the NSF-funded National Nanotechnology Infrastructure Network.

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New Blood Analysis Chip Could Lead to Disease Diagnosis in Minutes

The researchers have dubbed the device SIMBAS, which stands for Self-powered Integrated Microfluidic Blood Analysis System. SIMBAS appeared as the cover story March 7 in the peer-reviewed journalLab on a Chip.

"The dream of a true lab-on-a-chip has been around for a while, but most systems developed thus far have not been truly autonomous," said Ivan Dimov, UC Berkeley post-doctoral researcher in bioengineering and co-lead author of the study."By the time you add tubing and sample prep setup components required to make previous chips function, they lose their characteristic of being small, portable and cheap. In our device, there are no external connections or tubing required, so this can truly become a point-of-care system."

Dimov works in the lab of the study's principal investigator, Luke Lee, UC Berkeley professor of bioengineering and co-director of the Berkeley Sensor and Actuator Center.

"This is a very important development for global healthcare diagnostics," said Lee."Field workers would be able to use this device to detect diseases such as HIV or tuberculosis in a matter of minutes. The fact that we reduced the complexity of the biochip and used plastic components makes it much easier to manufacture in high volume at low cost. Our goal is to address global health care needs with diagnostic devices that are functional, cheap and truly portable."

For the new SIMBAS biochip, the researchers took advantage of the laws of microscale physics to speed up processes that may take hours or days in a traditional lab. They note, for example, that the sediment in red wine that usually takes days to years to settle can occur in mere seconds on the microscale.

The SIMBAS biochip uses trenches patterned underneath microfluidic channels that are about the width of a human hair. When whole blood is dropped onto the chip's inlets, the relatively heavy red and white blood cells settle down into the trenches, separating from the clear blood plasma. The blood moves through the chip in a process called degas-driven flow.

For degas-driven flow, air molecules inside the porous polymeric device are removed by placing the device in a vacuum-sealed package. When the seal is broken, the device is brought to atmospheric conditions, and air molecules are reabsorbed into the device material. This generates a pressure difference, which drives the blood fluid flow in the chip.

In experiments, the researchers were able to capture more than 99 percent of the blood cells in the trenches and selectively separate plasma using this method.

"This prep work of separating the blood components for analysis is done with gravity, so samples are naturally absorbed and propelled into the chip without the need for external power," said Dimov.

The team demonstrated the proof-of-concept of SIMBAS by placing into the chip's inlet a 5-microliter sample of whole blood that contained biotin (vitamin B7) at a concentration of about 1 part per 40 billion.

"That can be roughly thought of as finding a fine grain of sand in a 1700-gallon sand pile," said Dimov.

The biodetectors in the SIMBAS chip provided a readout of the biotin levels in 10 minutes.

"Imagine if you had something as cheap and as easy to use as a pregnancy test, but that could quickly diagnose HIV and TB," said Benjamin Ross, a UC Berkeley graduate student in bioengineering and study co-author."That would be a real game-changer. It could save millions of lives."

"The SIMBAS platform may create an effective molecular diagnostic biochip platform for cancer, cardiac disease, sepsis and other diseases in developed countries as well," said Lee.

Other co-lead authors of the study are Lourdes Basabe-Desmonts, senior scientist at Dublin City University's Biomedical Diagnostics Institute, and Jose L. Garcia-Cordero, currently post-doctoral scientist atÉcole Polytechnique Fédérale de Lausanne (EPFL Switzerland). Antonio J. Ricco, adjunct professor at the Biomedical Diagnostics Institute at Dublin City University, also co-authored the study.

The work was funded by the Science Foundation Ireland and the U.S. National Institutes of Health.

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Extremely Fast Magnetic Random Access Memory (MRAM) Computer Data Storage Within Reach

An invention made by the Physikalisch-Technische Bundesanstalt (PTB) changes this situation: A special chip connection, in association with dynamic triggering of the component, reduces the response from -- so far -- 2 ns to below 500 ps. This corresponds to a data rate of up to 2 GBit (instead of the approx. 400 MBit so far). Power consumption and the thermal load will be reduced, as well as the bit error rate. The European patent is just being granted this spring; the US patent was already granted in 2010. An industrial partner for further development and manufacturing such MRAMs under licence is still being searched for.

Fast computer storage chips like DRAM and SRAM (Dynamic and Static Random Access Memory) which are commonly used today, have one decisive disadvantage: in the case of an interruption of the power supply, the information stored on them is irrevocably lost. The MRAM promises to put an end to this. In the MRAM, the digital information is not stored in the form of an electric charge, but via the magnetic alignment of storage cells (magnetic spins). MRAMs are very universal storage chips because they allow -- in addition to the non-volatile information storage -- also faster access, a high integration density and an unlimited number of writing and reading cycles.

However, the current MRAM models are not yet fast enough to outperform the best competitors. The time for programming a magnetic bit amounts to approx. 2 ns. Whoever wants to speed this up, reaches certain limits which have something to do with the fundamental physical properties of magnetic storage cells: during the programming process, not only the desired storage cell is magnetically excited, but also a large number of other cells. These excitations -- the so-called magnetic ringing -- are only slightly attenuated, their decay can take up to approx. 2 ns, and during this time, no other cell of the MRAM chip can be programmed. As a result, the maximum clock rate of MRAM is, so far, limited to approx. 400 MHz.

Until now, all experiments made to increase the velocity have led to intolerable write errors. Now, PTB scientists have optimized the MRAM design and integrated the so-called ballistic bit triggering which has also been developed at PTB. Here, the magnetic pulses which serve for the programming are selected in such a skilful way that the other cells in the MRAM are hardly magnetically excited at all. The pulse ensures that the magnetization of a cell which is to be switched performs half a precision rotation (180°), while a cell whose storage state is to remain unchanged performs a complete precision rotation (360°). In both cases, the magnetization is in the state of equilibrium after the magnetic pulse has decayed, and magnetic excitations do not occur any more.

This optimal bit triggering also works with ultra-short switching pulses with a duration below 500 ps. The maximum clock rates of the MRAM are, therefore, above 2 GHz. In addition, several bits can be programmed at the same time which would allow the effective write rate per bit to be increased again by more than one order. This invention allows clock rates to be achieved with MRAM which can compete with those of the fastest volatile storage components.

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'Nano-Velcro' Technology Used to Improve Capture of Circulating Cancer Cells

Metastasis is the most common cause of cancer-related death in patients with solid tumors and occurs when these marauding tumor cells leave the primary tumor site and travel through the blood stream to set up colonies in other parts of the body.

The current gold standard for determining the disease status of tumors involves the invasive biopsy of tumor samples, but in the early stages of metastasis, it is often difficult to identify a biopsy site. By capturing CTCs in blood samples, doctors can essentially perform a"liquid" biopsy, allowing for early detection and diagnosis, as well as improved monitoring of cancer progression and treatment responses.

In a study published this month and featured on the cover of the journalAngewandte Chemie,the UCLA researchers announce the successful demonstration of this"nano-Velcro" technology, which they engineered into a 2.5-by-5-centimeter microfluidic chip. This second-generation CTC-capture technology was shown to be capable of highly efficient enrichment of rare CTCs captured in blood samples collected from prostate cancer patients.

The new approach could be even faster and cheaper than existing methods, and it captures a greater number of CTCs, the researchers said.

The prostate cancer patients were recruited with the help of a clinical team led by physicians Dr. Matthew Rettig, of the UCLA Department of Urology, and Dr. Jiaoti Huang, of the UCLA Department of Pathology and Laboratory Medicine.

The new CTC enrichment technology is based on the research team's earlier development of 'fly-paper' technology, outlined in a 2009 paper in Angewandte Chemie. The technology involves a nanopillar-covered silicon chip whose"stickiness" resulted from the interaction between the nanopillars and nanostructures on CTCs known as microvilli, creating an effect much like the top and bottom of Velcro.

The new, second-generation device adds an overlaid microfluidic channel to create a fluid flow path that increases mixing. In addition to the Velcro-like effect from the nanopillars, the mixing produced by the microfluidic channel's architecture causes the CTCs to have greater contact with the nanopillar-covered floor, further enhancing the device's efficiency.

"The device features high flow of the blood samples, which travel at increased (lightning) speed," said senior study author Dr. Hsian-Rong Tseng, an associate professor of molecular and medical pharmacology at the UCLA Crump Institute for Molecular Imaging and the California NanoSystems Institute at UCLA.

"The cells bounce up and down inside the channel and get slammed against the surface and get caught," explained Dr. Clifton Shen, another study author.

The advantages of the new device are significant. The CTC-capture rate is much higher, and the device is easier to handle than its first-generation counterpart. It also features a more user-friendly, semi-automated interface that improves upon the earlier device's purely manual operation.

"This new CTC technology has the potential to be a powerful new tool for cancer researchers, allowing them to study cancer evolution by comparing CTCs with the primary tumor and the distant metastases that are most often lethal," said Dr. Kumaran Duraiswamy, a graduate of UCLA Anderson School of Management who became involved in the project while in school."When it reaches the clinic in the future, this CTC-analysis technology could help bring truly personalized cancer treatment and management."

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Nanofabrication Tools May Make Silicon Optical Chips More Accessible

Silicon optical chips are critical to the Air Force because of their size, weight, power, rapid cycle time, program risk reduction and the improvements they can offer in data communications, lasers and detectors.

The Air Force Office of Scientific Research is funding this effort in silicon photonics called"Optoelectronic Systems Integration in Silicon" at UW's Nanophotonics Lab in Seattle. OpSIS is hosted by UW's Institute for Photonic Integration. Hochberg is in charge of the OpSIS research program, the Nanophotonics Lab and the Institute for Photonic Integration.

Hochberg emphasizes that the funding from the Air Force Research Laboratory and AFOSR is a critical component in getting the effort off the ground because it provides both a strong technical validation, and the resources to get started on the project.

Unlike most research groups that are designing, building and testing silicon photonic devices or optical chips in-house rather than by using commercial chip fabrication facilities, the UW researchers are using shared infrastructure at the foundry at BAE Systems in Manassas, Virginia. There they are working toward creating high-end, on-shore manufacturing capabilities that will be ultimately made available to the wider community. In the past few years, complex photonic circuitry has not been accessible to researchers because of the expense and a lack of standard processes.

The UW researchers are working on system design and validation so they can imitate what's been done in electronics by stabilizing and characterizing some processes so that the transition from photonics to systems can be smooth.

"The OpSIS program will help advance the field of silicon photonics by bringing prototyping capability within reach of startup companies and researchers," said Hochberg."They will provide design rules, device design support and design-flow development so that even non-experts will be able to design and integrate photonics and electronics."

Silicon photonics has developed over the last decade, and the transition from using devices to systems is something that has only recently occurred.

"The digital electronics revolution over the past 40 years has had a transformative effect on how the Air Force systems are built, and we're hoping to have a similar impact on photonic systems," he said.

The researchers' current goal is to work first on test runs for the new optical chips for commercial uses and on developing some software tools that will make the design process easier.

AFOSR program manager, Dr. Gernot S. Pomrenke, agrees with Prof. Hochberg."Integrating silicon photonics will impact Air Force, DoD and commercial avionics," he said."AFRL has been a leader in developing and supporting this technology over the last two decades and the OpSIS program will help in transitioning silicon photonics into new system capabilities."

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Surgical Instruments With Electronic Serial Numbers

Be it a heart transplant or a Cesarean section, every operation requires a wide variety of surgical instruments, from simple retractors, clamps, scalpels and scissors to more specialist devices such as cerclage wire passers, which surgeons employ to repair long, oblique fractures in bones. These are shaped in such a way as to half encircle the broken bone, and incorporate a hollow channel. In a process not unlike stringing a parcel for posting, thread or wire is fed through the channel around the damaged bone and then knotted in place, both to support the bone and to hold the broken parts together."Until now, it has always been time-consuming and expensive to manufacture surgical instruments featuring this kind of channel," says Claus Aumund-Kopp of the Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Bremen. Because it is nigh-on impossible to machine curved channels, shaped tubes have traditionally had to be cast, or else welded or soldered retrospectively.

At the MEDTEC Europe trade show in Stuttgart from March 22 through 24, the Bremen-based scientists will be presenting a technique that enables the manufacture of surgical instruments of any shape, even those with complex interiors like channels, or those with integrated RFID chips. The technique in question is laser melting. Originally developed for the production of industrial prototypes, this manufacturing method uses an extremely fine laser beam to melt a powder material into almost any desired form, one layer at a time.

"Nowadays, laser melting is a mature technology, which has already proved its worth in the manufacture of medical implants," states Aumund-Kopp. Like all generative -- i.e. bottom-up -- manufacturing techniques, it has two major advantages: First, unlike in turning, drilling or milling, hardly any material is wasted; and second, there are no production-related restrictions on the shape or interior structure of the workpiece."The designer can focus exclusively on the surgeon's stated requirements," says the engineer. For surgical instruments, either cobalt-chromium steel or titanium powders could be used -- both are standard materials in generative manufacturing. Although no-one has yet begun using the laser melting technique to produce surgical instruments, Aumund-Kopp believes it would be an ideal manufacturing method:"Even small quantities of customized surgical instruments incorporating completely new functions could easily be produced in this way," he reports. 3-dimensional model on a computer is the only template needed; intermediate stages, including the production of special tools or casting molds, are eliminated.

Steel components that are produced using laser melting technology also demonstrate particular electrical properties. Normally, metals shield against electromagnetic radiation such as radio waves, so whenever an RFID chip is cast in metal, a small opening must be left above it, otherwise it will not be readable. But this is not necessary with laser-melted instruments; even though they are completely shrouded in metal, the integrated RFID chips are still able to transmit and receive over short distances."We assume that the layered structure of the material shapes the field in such a way that the chips remain readable despite their metal covering," explains Aumund-Kopp. This could prove advantageous in the operating room: After every operation, all surgical instruments have to be cleaned, sterilized and counted; if they had integrated RFID chips, quantities and individual numerical codes could be checked quickly and easily and could be electronically linked to the operation report or to specific instrument data such as date of manufacture, protocols for use or current state of cleanliness.

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Plug-and-Play Multi-Core Voltage Regulator Could Lead to 'Smarter' Smartphones, Slimmer Laptops and Energy-Friendly Data Centers

Today's consumers expect mobile devices that are increasingly small, yet ever-more powerful. All the bells and whistles, however, suck up energy, and a phone that lasts only 4 hours because it's also a GPS device is only so much use.

To promote energy-efficient multitasking, Harvard graduate student Wonyoung Kim has developed and demonstrated a new device with the potential to reduce the power usage of modern processing chips.

The advance could allow the creation of"smarter" smartphones, slimmer laptops, and more energy-friendly data centers.

Kim's on-chip, multi-core voltage regulator (MCVR) addresses what amounts to a mismatch between power supply and demand.

"If you're listening to music on your MP3 player, you don't need to send power to the image and graphics processors at the same time," Kim says."If you're just looking at photos, you don't need to power the audio processor or the HD video processor."

"It's like shutting off the lights when you leave the room."

Kim's research at Harvard's School of Engineering and Applied Sciences (SEAS) showed in 2008 that fine-grain voltage control was a theoretical possibility. This month, he presented a paper at the Institute of Electrical and Electronics Engineers' (IEEE) International Solid-State Circuits Conference (ISSCC) showing that the MCVR could actually be implemented in hardware.

Essentially a DC-DC converter, the MCVR can take a 2.4-volt input and scale it down to voltages ranging from 0.4 to 1.4V. Built for speed, it can increase or decrease the output by 1V in under 20 nanoseconds.

The MCVR also uses an algorithm to recognize parts of the processor that are not in use and cuts power to them, saving energy. Kim says it results in a longer battery life (or, in the case of stationary data centers, lower energy bills), while providing the same performance.

The on-chip design means that the power supply can be managed not just for each processor chip, but for each individual core on the chip. The short distance that signals then have to travel between the voltage regulator and the cores allows power scaling to happen quickly -- in a matter of nanoseconds rather than microseconds -- further improving efficiency.

Kim has obtained a provisional patent for the MCVR with his Ph.D. co-advisers at SEAS, Gu-Yeon Wei, Gordon McKay Professor of Electrical Engineering, and David Brooks, Gordon McKay Professor of Computer Science, who are coauthors on the paper he presented this week.

"Wonyoung Kim's research takes an important step towards a higher level of integration for future chips," says Wei."Systems today rely on off-chip, board-level voltage regulators that are bulky and slow. Integrating the voltage regulator along with the IC chip to which it supplies power not only reduces broad-level size and cost, but also opens up exciting opportunities to improve energy efficiency."

"Kim's three-level design overcomes issues that hamper traditional buck and switch-capacitor converters by merging good attributes of both into a single structure," adds Brooks."We believe research on integrated voltage regulators like Kim's will be an essential component of future computing devices where energy-efficient performance and low cost are in demand."

Although Kim estimates that the greatest demand for the MCVR right now could be in the market for mobile phones, the device would also have applications in other computing scenarios. Used in laptops, the MCVR might reduce the heat output of the processor, which is currently one barrier to making slimmer notebooks. In stationary scenarios, the rising cost of powering servers of ever-increasing speed and capacity could be reduced.

"This is a plug-and-play device in the sense that it can be easily incorporated into the design of processor chips," says Kim."Including the MCVR on a chip would add about 10 percent to the manufacturing cost, but with the potential for 20 percent or more in power savings."

The research was supported by the National Science Foundation's Division of Computer and Network Systems and Division of Computing and Communication Foundations.

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Fingerprint Makes Computer Chips Counterfeit-Proof

Fraunhofer researchers will be presenting a prototype at the embedded world Exhibition& Conference in Nuremberg from March 1 to 3.

Product piracy long ago ceased to be limited exclusively to the consumer goods sector. Industry, too, is increasingly having to combat this problem. Cheap fakes cost business dear: The German mechanical and plant engineering sector alone lost 6.4 billion euros of revenue in 2010, according to a survey by the German Engineering Federation (VDMA). Sales losses aside, low-quality counterfeits can also damage a company's brand image. Worse, they can even put people's lives at risk if they are used in areas where safety is paramount, such as automobile or aircraft manufacture. Patent rights or organizational provisions such as confidentiality agreements are no longer sufficient to prevent product piracy. Today's commercially available anti-piracy technology provides a degree of protection, but it no longer constitutes an insurmountable obstacle for the product counterfeiters: Criminals are using scanning electron microscopes, focused ion beams or laser bolts to intercept security keys -- and adopting increasingly sophisticated methods.

No two chips are the same

At embedded world, researchers from the Fraunhofer Institute for Secure Information Technology SIT will be demonstrating how electronic components or chips can be made counterfeit-proof using physical unclonable functions (PUFs)."Every component has a kind of individual fingerprint since small differences inevitably arise between components during production," explains Dominik Merli, a scientist at Fraunhofer SIT in Garching near Munich. Printed circuits, for instance, end up with minimal variations in thickness or length during the manufacturing process. While these variations do not affect functionality, they can be used to generate a unique code.

Invasive attacks destroy the structure

A PUF module is integrated directly into a chip -- a setup that is feasible not only in a large number of programmable semiconductors known as FPGAs (field programmable gate arrays) but equally in hardware components such as microchips and smartcards."At its heart is a measuring circuit, for instance a ring oscillator. This oscillator generates a characteristic clock signal which allows the chip's precise material properties to be determined. Special electronic circuits then read these measurement data and generate the component-specific key from the data," explains Merli. Unlike conventional cryptographic processes, the secret key is not stored on the hardware but is regenerated as and when required. Since the code relates directly to the system properties at any given point in time, it is virtually impossible to extract and clone it. Invasive attacks on the chip would alter physical parameters, thus distorting or destroying the unique structure.

The Garching-based researchers have already developed two prototypes: A butterfly PUF and a ring oscillator PUF. At present, these modules are being optimized for practical applications. The experts will be at embedded world in Nuremberg (hall 11, stand 203) from March 1-3 to showcase FPGA boards that can generate an individual cryptographic key using a ring oscillator PUF. These allow attack-resistant security solutions to be rolled out in embedded systems.

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New Lab-on-Chip Advance Uses Low-Cost, Disposable Paper Strips

The innovation represents a way to enhance commercially available diagnostic devices that use paper-strip assays like those that test for diabetes and pregnancy.

"With current systems that use paper test strips you can measure things like pH or blood sugar, but you can't perform more complex chemical assays," said Babak Ziaie, a Purdue University professor of electrical and computer engineering and biomedical engineering."This new approach offers the potential to extend the inexpensive paper-based systems so that they are able to do more complicated multiple analyses on the same piece of paper. It's a generic platform that can be used for a variety of applications."

Findings are detailed in a research paper published online in the journalLab on a Chip.

Current lab-on-a-chip technology is relatively expensive because chips must be specifically designed to perform certain types of chemical analyses, with channels created in glass or plastic and tiny pumps and valves directing the flow of fluids for testing.

The chips are being used for various applications in medicine and research, measuring specific types of cells and molecules in a patient's blood, monitoring microorganisms in the environment and in foods, and separating biological molecules for laboratory analyses. But the chips, which are roughly palm-size or smaller, are difficult to design and manufacture.

The new technique is simpler because the testing platform will be contained on a disposable paper strip containing patterns created by a laser. The researchers start with paper having a hydrophobic -- or water-repellant -- coating, such as parchment paper or wax paper used for cooking.

"We can buy this paper at any large discount retail store," Ziaie said."These patterns can be churned out in the millions at very low cost."

A laser is used to burn off the hydrophobic coatings in lines, dots and patterns, exposing the underlying water-absorbing paper only where the patterns are formed.

"Since the hydrophobic agent is already present throughout the thickness of the paper, our method creates islands of hydrophilic patterns," Ziaie said."This modified surface has a highly porous structure, which helps to trap and localize chemical and biological aqueous reagents for analysis. Furthermore, we've selectively deposited silica microparticles on patterned areas to allow diffusion from one end of a channel to the other."

Those microparticles help to wick liquid to a location where it would combine with another chemical, called a reactant, causing it to change colors and indicating a positive or negative test result.

Having a patterned hydrophilic surface is needed for many detection methods in biochemistry, such as enzyme-linked immunosorbent assay, or ELISA, used in immunology to detect the presence of an antibody or an antigen in a sample, Ziaie said.

To demonstrate the new concept, the researchers created paper strips containing arrays of dots dipped in luminol, a chemical that turns fluorescent blue when exposed to blood.

"Then we sprayed blood on the strips, showing the presence of hemoglobin," said Ziaie, whose research is based at the Birck Nanotechnology Center in the university's Discovery Park."This is just a proof of concept."

Laser modification is known to alter the"wettability" of materials by causing structural and chemical changes to surfaces. However, this treatment has never before been done on paper, he said.

The researchers performed high-resolution imaging and spectroscopic analysis to study the mechanism behind the hydrophobic-hydrophilic conversion of laser-treated parchment paper.

The new approach is within a research area called paper microfluidics.

"Other techniques in paper microfluidics are more complicated," Ziaie said.

For example, other researchers have developed a method that lays down lines of wax or other hydrophobic material on top of untreated, hydrophilic paper.

"Our process is much easier because we just use a laser to create patterns on paper you can purchase commercially and it is already impregnated with hydrophobic material," Ziaie said."It's a one-step process that could be used to manufacture an inexpensive diagnostic tool for the developing world where people can't afford more expensive analytical technologies."

The strips might be treated with chemicals that cause color changes when exposed to a liquid sample, with different portions of the pattern revealing specific details about the content of the sample. One strip could be used to conduct dozens of tests, he said.

The strips might be inserted into an electronic reader, similar to technology used in conventional glucose testers. Color changes would indicate the presence or absence of specific chemical compounds.

The research paper was written by graduate students Girish Chitnis, Zhenwen Ding and Chun-Li Chang; Cagri A. Savran, an associate professor of mechanical engineering, biomedical engineering and electrical and computer engineering; and Ziaie.

The National Science Foundation funded the work.

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